The present invention relates to formulations of organophosphate pesticides. In particular, the invention provides microencapsulated formulations of the insecticide/nematicide, cadusafos, that are equally effective, yet reduced in toxicity, as compared with conventional formulations.
The organophosphate compound, S,S-di-sec-butyl-O-ethyl phosphorodithioate (cadusafos), is an effective insecticide and nematicide. However, the toxicity of cadusafos impairs its safe use. For instance, a 100 g/l aqueous microemulsion formulation of cadusafos presently in commercial use recommends that the user wear complete body protection for handling and applying the formulation. The labeling also indicates that the formulation is highly toxic to mammals, fish, arthropods and birds.
Accordingly, a need exists to develop formulations of cadusafos that maintain its effectiveness as an insecticide or nematicide, but reduce its toxicity to mammals, birds, fish and other non-target organisms. Such formulations would improve safety to humans and would minimize any negative impact on the environment resulting from use of this compound.
Provided in accordance with the present invention are pesticidally effective, microencapsulated formulations of cadusafos having low or moderate toxicity to non-target organisms, among other advantages.
According to one aspect of the invention, the formulation comprises an aqueous suspension of microcapsules, which are composed of a polyurea shell surrounding a core of the cadusafos. The polyurea shell is formed from interfacial polymerization of a polyisocyanate and one or more polyfunctional amines, the polyurea. shell being sufficiently impenetrable to the cadusafos so as to effect the aforementioned reduction in mammalian toxicity of the formulation, as compared with known aqueous microemulsion cadusafos formulations of an equivalent or lesser cadusafos concentration.
According to another aspect of the invention, a granular cadusafos formulation is provided, which comprises the aforementioned microcapsules containing cadusafos affixed to a granular carrier.
Also provided in accordance with the present invention are processes for making the aforementioned aqueous capsule suspension (CS) or granular microencapsulated cadusafos formulations.
The microencapsulated cadusafos of the present invention possesses lower skin, oral, and inhalation toxicity to mammals, thereby enabling safer handling and use of the pesticide. According to United States Environmental Protection Agency (xe2x80x9cEPAxe2x80x9d) guidelines, the formulations of the present invention are rated as Category II (warning) or Category III (caution) compositions at twice the concentration of non-microencapsulated liquid formulations of the same active ingredient, which are rated as Category II. The microencapsulated formulations exhibit no loss of pesticidal activity or physical and chemical stability as compared to non-microencapsulated formulations. In addition, the microencapsulated formulations of the present invention are consistent in color, which is not the case in aqueous microemulsion formulations of the compound if the technical cadusafos is pre-treated with copper salts to remove unpleasant odor for commercial use.
The microencapsulated cadusafos of the invention is made according to the following basic steps: (a) providing an aqueous phase (also referred to herein as a xe2x80x9ccontinuousxe2x80x9d phase) containing an emulsifier and an antifoam agent; (b) providing a water-immiscible phase (also referred to herein as a xe2x80x9cdiscontinuousxe2x80x9d phase) containing the cadusafos along with a first polyfunctional compound; (c) emulsifying the aqueous phase with the water-immiscible phase to form a dispersion of water-immiscible droplets in the aqueous phase; and (d) adding to the dispersion, either neat or in an aqueous solution, a second polyfunctional compound, thus forming a polymeric shell known herein as a microcapsule, around the water-immiscible droplets; i.e., forming microcapsules of cadusafos The first polyfunctional compound is any suitable compound having two or more reactive groups, such as, but not limited to, an isocyanate monomer. The second polyfunctional compound is any suitable compound having two or more reactive groups, such as, but not limited to, a polyfunctional amine; wherein the first and second polyfunctional compounds are different. The suitability of the first and second polyfunctional compounds is that they have the ability to form a heteromeric structure at the interface between the dispersed cadusafos and the aqueous phase. Such compounds will include both hydrophobic and hydrophilic groups between the two compounds, such that such groups can both be in a single such compound or can be exclusive to one or the other such compound. The last step is referred to as interfacial polymerization due to the fact that the polyurea shell is formed by polymerization of the first and second polyfunctional compounds, which are preferably an isocyanate and a polyfunctional amine(s) at the interface of the water-immiscible phase (the droplets) and the aqueous phase, thereby forming, predferably, a polyurea shell.
Once the microcapsules are formed, the suspension is preferably cured, i.e., moderately heated to complete polymerization, after which one or more additives, such as propylene glycol, xanthan gum, urea, bactericides, amphoteric surfactants, inert dyes or ionic dispersing agents (e.g., alkyl naphthalene sulfonate), may be added.
The addition of materials after encapsulation and curing to adjust viscosity, stability and suspension/dispersion characteristics preferably do not affect the reduction of toxicity or the pesticidal efficacy of the formulation. A preferred further step comprises adjusting the pH of the formulation to neutral, i.e., from about pH 6.5 to about pH 7.5, which results in improved stability. The use of the modifier xe2x80x9caboutxe2x80x9d with respect to pH is used herein to indicate a variance of at least one-half a pH unit, and preferably indicates a variance of one-half a pH unit. In other contexts herein where the modifier xe2x80x9caboutxe2x80x9d is used to qualify a non-log unit, the xe2x80x9caboutxe2x80x9d is intended to indicate a variance of xc2x115%, yet more preferably a variance of xc2x110%.
The aqueous phase ordinarily contains about 0.3 to about 3.0, preferably about 0.7 to about 2.5, weight percent of one or more emulsifiers. The emulsifier preferred for use in the present invention is polyvinyl alcohol. Other emulsifiers suitable for use in the present invention include, but are not limited to, nonylphenol ethoxylate, sorbitan mono- and trioleate, and ethoxylated oleate.
The aqueous phase also contains about 0.1 to about 1.0, preferably about 0.3 to about 0.9 weight percent of one or more antifoam agents. Antifoam agents suitable for use in the present invention include, but are not limited to, silicon based antifoam agents such as Dow Corning Antifoam DC1500 and DC1520.
The aqueous phase optionally may also include a viscosity modifier/stabilizer, such as xanthan gum from about 0.05 to about 0.50, preferably about 0.06 to about 0.40, weight percent, as well as one or more bactericides from about 0.02 to about 0.10, preferably about 0.03 to about 0.05, weight percent. Bactericides useful for the present invention include, but are not limited to, Legend MK (Rohm and Haas Co.), Proxel GXL (Zeneca, Inc.) and Dowicide A (Dow Chemical).
The water-immiscible phase (also referred to in the examples as the polyisocyanate solution) ordinarily contains from about 50 to about 98, preferably about 53 to about 92 weight percent cadusafos and about 2 to about 35, preferably about 4 to about 25, weight percent of the first polyfunctional compound, preferably an isocyanate monomer. Polymethylene polyphenyl isocyanate (PMPPI) is particularly preferred for use in the present invention; e.g., Mondur MR (Miles, Inc.), Papi 27 or 135 (Dow Chemical) and Desmodur (Bayer). Other suitable first polyfunctional compounds can also be used in accordance with the invention, provided they possess appropriate chemical and physical characteristics (e.g., chain length, functionality) such that the polymeric shell formed around the cadusafos acts as a barrier to egress of the cadusafos from the microcapsules. Appropriate first polyfunctional compounds will be apparent to persons skilled in the art.
The water-immiscible phase also may contain a hydrocarbon solvent, such as, for example, a vegetable oil. However, the solvent is optional in the preparation of microcapsule formulations of cadusafos, particularly with respect to such formulations containing more than about 240 grams cadusafos per liter. Hydrocarbon solvents useful in the practice of the present invention include, but are not limited to, petroleum hydrocarbons such as Aromatic 200, Aromatic 150 and Exxate 1000 (all from Exxon Chemicals), or vegetable oils, such as corn oil. The solvent, if any is used, is present at about 15 to about 30, preferably about 20 to about 25, weight percent of the water-immiscible phase.
One advantage of the present invention is that the formulations can be prepared with either untreated cadusafos or with cadusafos that has been treated with a copper salt. Copper salts are added to cadusafos to reduce its odor. Typically, copper salts interfere with the formation of microcapsules by interfacial polymerization, but this is found not to be the case in the present process.
The second polyfunctional compound solution ordinarily contains about 10 to about 100, preferably about 20 to about 70, weight percent of a second polyfunctional compound or mixture of such second polyfunctional compounds. Examples of suitable second polyfunctional compounds that are useful for practice of the present invention include various polyfunctional amines, such as, but not limited to: diethylenetriamine (DETA), triethylenetetramine (TETA), and 1,6-hexanediamine (HDA).
Interfacial polymerization of the first and second polyfunctional compounds forms the polymeric microcapsules surrounding the cadusafos according to the following exemplary chemistry using PMPPI as the first polyfunctional compound and a generic amine for the second polyfunctional compound: 
Wherein A is PMPPI with an average functionality of about 2.3 to about 2.6 and B is a polyfunctional amine.
Several parameters of the process of the invention contribute to the characteristics of the final formulation. The emulsification step preferably is effected using high shear mixing to yield small droplets of the immiscible phase. The average size of the microcapsules of the invention is about 5 to about 25 xcexcm. Factors that influence the size of the microcapsules, as well as the stability of the emulsion, include: (1) total amount of shear applied during the emulsification; (2) type and amount of surfactant or hydrocarbon solvent in the discontinuous phase, if any are used; (3) temperature or viscosity of the mixture; and (4) presence and amount of xanthan gum or alkyl naphthalene sulfonate dispersing agent in the mixture, if any.
Selection of relative percentages of first and second polyfunctional compound monomers (e.g., PMPPI and amines) in the discontinuous phase to achieve the appropriate microencapsulation requires a balance among competing factors. In general, increasing the percentage of the monomers in the discontinuous phase decreases toxicity of the final formulation. Likewise, decreasing the percentage of monomers results in higher toxicity of the final formulation. In an optimum general formulation of the invention, a balance of high efficacy and low toxicity is achieved by including about 5 to about 35, preferably about 7 to about 30, weight percent of monomers in the discontinuous phase. The operating conditions needed to yield microcapsules from the appropriate monomer concentrations depends upon the emulsifying equipment used; the determination of such conditions is well within the level of skill in the art.
In contrast to the vigorous conditions needed for the emulsification step, agitation during addition of the second polyfunctional compound should be low-shear, as accomplished through use of a mechanical paddle stirrer. After the second polyfunctional compound has been added, stirring is continued while the suspension is cured, e.g., by heating to a temperature of about 20 to about 60xc2x0 C., preferably from about 30 to about 50xc2x0 C., for about one to about 10 hours, preferably about three to about four hours.
One or more substances may be added to the formulation after encapsulation is complete. These typically are selected from the following, though other substances not specifically listed will be apparent to persons skilled in the art (1) propylene glycol, preferably from about 1.3 to about 6.0 weight percent; (2) urea, preferably from about 5.0 to about 5.5 weight percent; (3) xanthan gum, preferably from about 0.003 to about 0.30 weight percent; (4) one or more bactericides to a total weight percent of about 0.01 to about 0.10; (5) one or more inert dyes at a total weight percent up to about 0.05; and (6) one or more surfactants up to a total weight percent of about 7.0; each weight percent relative to the weight of the formulation after addition of the additives.
The preferred practice, after curing the microcapsules, is to neutralize the formulation, e.g., with phosphoric, acetic or hydrochloric acid, although other acids will suffice. The post-encapsulation additives are then added, and stirring of the formulation continued for about four hours at a moderately heated temperature (e.g., 50xc2x0 C.).
Capsule Suspension (CS) formulations of cadusafos prepared by the above-described methods have the following general compositional features: they contain from about 150 to about 360 grams cadusafos per liter of formulation, and comprise an aqueous suspension of microcapsules made up of a polyurea shell surrounding a core of cadusafos and, optionally, a hydrocarbon solvent, and further comprise an emulsifier, such as about 0.3 to about 3.0 weight percent polyvinyl alcohol, and an antifoam agent at about 0.05 to about 0.5 weight percent. The formulation also may optionally contain about 0.06 to about 0.4 weight percent xanthan gum or other viscosity modifier/stabilizer, about 0.02 to about 0.10 weight percent of one or more bactericides, about 0.7 to about 6.7 weight percent of one or more surfactants, and about 1.2 to about 5.8 weight percent of propylene glycol or urea, or a combination thereof. Preferred formulations contain about 200 g/l cadusafos,-comprising about 53 to about 92 weight percent cadusafos and about 4 to about 25 weight percent PMPPI in the water-immiscible phase, and utilizing DETA, TETA or HDA as the polyfunctional amine.
In another aspect of this invention, the above-described CS cadusafos formulations are used to prepare granular microemulsion (G-ME) formulations of cadusafos. The G-ME formulations are prepared by the following steps: (a) provide a homogeneous mixture of the microencapsulated or capsule suspension (CS) cadusafos formulation and an adhesive agent; b) disperse the mixture onto a carrier; and c) allow the carrier to dry, thereby forming the granular formulation.
The G-ME formulation will ordinarily contain about 5.0 to about 30.0, preferably about 10.0 to about 20.0, weight percent of cadusafos CS formulation, about 60.0 to about 95.0, preferably about 70.0 to about 80.0, weight percent of a carrier, and about 0.05 to about 5.0, preferably about 0.1 to about 2.0, weight percent of an adhesive agent.
Adhesive agents useful for the practice of the invention include, but are not limited to, calcium and sodium lignosulfonates, polyalkylene glycols, and other polymer solutions, such as resins. Other suitable adhesives will be readily apparent to persons of skill in the art.
Examples of carriers that may be used in the present invention include, but are not limited to, cellulose complexes, attapulgite clays, silica complexes, and plant materials, such as corn cobs. Other suitable carriers will be readily apparent to persons of skill in the art.
The time required for the mixture of the CS formulation and the adhesive to reach homogeneity is not critical, but is usually from about one to about ten minutes. Dispersion onto the carrier continues until the entire mixture is exhausted. The granular formulation is then dried for several hours.